Chemoradiotherapy With or Without Simultaneous Integrated Boost for Cervical Cancer With Full-Thickness Stromal Invasion: A Phase 3 Randomized Clinical Trial.

IMPORTANCE

Patients with cervical cancer exhibiting full-thickness (FT) and outer full-thickness (OFT) stromal invasion after radical hysterectomy face high risks of recurrence, yet optimal adjuvant radiotherapy strategies remain debated.

OBJECTIVE

To determine if simultaneous integrated boost (SIB) radiotherapy increases 3-year progression-free survival (PFS) by 13% vs conventional chemoradiotherapy (CRT) among patients with cervical cancer exhibiting FT or OFT stromal invasion after surgery.

DESIGN, SETTING, AND

PARTICIPANTS

This phase 3, single-center, randomized clinical superiority trial enrolled 466 patients in Shanghai Cancer Center with FIGO (International Federation of Gynecology and Obstetrics) 2018 stage IB to IIA and IIIC cervical cancer and pathologically confirmed FT or OFT stromal invasion from October 15, 2019, to September 20, 2024. Data were analyzed in October 2024.

INTERVENTIONS: Patients were randomized to receive conventional CRT (50.4 Gy in 28 fractions plus cisplatin, 40 mg/m2/wk) or CRT plus SIB radiotherapy (58.8 Gy in 28 fractions).

MAIN OUTCOMES AND MEASURES: The primary end point was 3-year PFS. Secondary end points included overall survival (OS), acute and late toxic effects, and progression patterns. All outcomes were analyzed under the intention-to-treat principle.

RESULTS

A total of 466 patients with cervical cancer presenting with FT or OFT stromal invasion after radical hysterectomy were randomized (233 in non-SIB radiotherapy group: median age, 53 years [IQR, 46-59 years]; 233 in SIB radiotherapy group: median age, 55 years [IQR, 48-60 years]). At a median follow-up of 33 months (range, 8-54 months), SIB radiotherapy significantly improved 3-year PFS compared with conventional CRT (84.6% vs 76.8%; P = .04), corresponding to a 35.7% reduction in progression risk (hazard ratio [HR], 0.64; 95% CI, 0.42-0.99; P = .04). Multivariable analysis identified adenocarcinoma (HR, 2.68; 95% CI, 1.62-4.44; P < .001), adenosquamous carcinoma (HR, 2.66; 95% CI, 1.06-6.66; P = .04), tumor size of 4 cm or more (HR, 1.81; 95% CI, 1.17-2.81; P = .01), lymphovascular space invasion (HR, 2.88; 95% CI, 1.45-5.72; P = .003), and positive vaginal margins (HR, 4.60; 95% CI, 1.97-10.73; P < .001) as independent risk factors of poorer PFS, while SIB radiotherapy remained protective (HR, 0.59; 95% CI, 0.38-0.91; P = .02). Profiles of toxic effects were comparable between groups.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of postoperative patients with cervical cancer presenting with FT or OFT stromal invasion, SIB radiotherapy significantly enhanced PFS without increased toxic effects. The clinical benefits and comparable profiles of toxic effects support its integration into adjuvant care.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900027272.